tbuckley/cabot-search huggingface dataset:
Associations between baseline heart rate and blood pressure and time to events in heart failure with reduced ejection fraction patients: Data from the <scp>QUALIFY</scp> international registry
Authors: Amr Abdin, Stefan D. Anker, Martin R. Cowie, Gerasimos S. Filippatos, Piotr Ponikowski, Luigi Tavazzi, Jakob Schöpe, Stefan Wagenpfeil, Michel Komajda, Michael Böhm
Journal: European Journal of Heart Failure (2023)

A high resting heart rate (RHR) and low systolic blood pressure (SBP) are a risk factor and a risk indicator, respectively, for poor heart failure (HF) outcomes. This analysis evaluated the associations between baseline RHR and SBP with outcomes and treatment patterns in patients with HF and reduced ejection fraction (HFrEF) in the QUALIFY (QUality of Adherence to guideline recommendations for LIFe-saving treatment in heart failure surveY) international registry.Between September 2013 and December 2014, 7317 HFrEF patients with a previous HF hospitalization within 1-15 months were enrolled in the QUALIFY registry. Complete follow-up data were available for 5138 patients. The relationships between RHR and SBP and outcomes were assessed using a Cox proportional hazards model and were analysed according to baseline values as high RHR (H-RHR) ≥75 bpm versus low RHR (L-RHR) <75 bpm and high SBP (H-SBP) ≥110 mmHg versus low SBP (L-SBP) <110 mmHg and analysed according to each of the following four phenotypes: H-RHR/L-SBP, L-RHR/L-SBP, H-RHR/H-SBP and L-RHR/H-SBP (reference group). Compared to the reference group, H-RHR/L-SBP was associated with the worst outcomes for the combined primary endpoint of cardiovascular death and HF hospitalization (hazard ratio [HR] 1.83, 95% confidence interval [CI] 1.51-2.21, p < 0.001), cardiovascular death (HR 2.70, 95% CI 1.69-4.33, p < 0.001), and HF hospitalization (HR 1.62, 95% CI 1.30-2.01, p < 0.001). Low-risk patients with L-RHR/H-SBP achieved more frequently ≥50% of target doses of angiotensin-converting enzyme inhibitors (ACEIs) and beta-blockers (BBs) than the other groups. However, 48% and 46% of low-risk patients were not well treated with ACEIs and BBs, respectively (≤50% of target dose or no treatment).In patients with HFrEF and recent hospitalization, elevated RHR and lower SBP identify patients at increased risk for cardiovascular endpoints. While SBP and RHR are often recognized as barriers that deter physicians from treating with high doses of recommended drugs, they are not the only reason leaving many patients suboptimally treated.
Reduced <scp>Cortico‐Cortical Resting‐State</scp> Connectivity in Sensory Systems Related to Bodily Pain in Juvenile Fibromyalgia
Authors: Maria Suñol, Jon Dudley, Michael F. Payne, Han Tong, Tracy V. Ting, Susmita Kashikar‐Zuck, Robert C. Coghill, Marina López‐Solà
Journal: Arthritis & Rheumatology (2023)

Juvenile-onset fibromyalgia (JFM) is a paradigmatic chronic pain condition for which the underlying neurobiological substrates are poorly understood. This study examined, for the first time, data-driven resting-state functional connectivity (rsFC) alterations in 37 female adolescents with JFM compared with 43 healthy female adolescents and identified associations with bodily pain.
CuS@TA‐Fe Nanoparticle‐Doped Multifunctional Hydrogel with Peroxide‐Like Properties and Photothermal Properties for Synergistic Antimicrobial Repair of Infected Wounds
Authors: Xiaohu Zhou, Tiantian Chen, Tengda Ma, Lizhao Yan, Haojie Wei, Shuang Liu, Zhiyin Dai, Zhizhong Xie, Jun Deng, Shengxiang Tao, Lihong Fan, Yingying Chu
Journal: Advanced Healthcare Materials (2023)

Bacterial infection is a critical factor in wound healing. Due to the abuse of antibiotics, some pathogenic bacteria have developed resistance. Thus, there is an urgent need to develop a non-antibiotic-dependent multifunctional wound dressing for the treatment of bacteria-infected wounds. In this work, a multifunctional AOCuT hydrogel embedded with CuS@TA-Fe nanoparticles (NPs) through Schiff base reaction between gelatin quaternary ammonium salt - gallic acid (O-Gel-Ga) and sodium dialdehyde alginate (ADA) along with electrostatic interactions with CuS@TA-Fe NPs is prepared. These composite hydrogels possess favorable injectability, rapid shape adaptation, electrical conductivity, photothermal antimicrobial activity, and biocompatibility. Additionally, the doped NPs not only impart fast self-healing properties and excellent adhesion performance to the hydrogels, but also provide excellent peroxide-like properties, enabling them to scavenge free radicals and exhibit anti-inflammatory and antioxidant capabilities via photothermal (PTT) and photodynamic (PDT) effects. In an S. aureus infected wound model, the composite hydrogel effectively reduces the expression level of wound inflammatory factors and accelerates collagen deposition, epithelial tissue, and vascular regeneration, thereby promoting wound healing. This safe and synergistic therapeutic system holds great promise for clinical applications in the treatment of infectious wounds.
Prediction of adult asthma risk in early childhood using novel adult asthma predictive risk scores
Authors: Abdal J. Farhan, Dilini M. Kothalawala, Ramesh J. Kurukulaaratchy, Raquel Granell, Angela Simpson, Clare Murray, Adnan Custovic, Graham Roberts, Hongmei Zhang, S. Hasan Arshad
Journal: Allergy (2023)

Abstract Background Numerous risk scores have been developed to predict childhood asthma. However, they may not predict asthma beyond childhood. We aim to create childhood risk scores that predict development and persistence of asthma up to young adult life. Methods The Isle of Wight Birth Cohort ( n = 1456) was prospectively assessed up to 26 years of age. Asthma predictive scores were developed based on factors during the first 4 years, using logistic regression and tested for sensitivity, specificity and area under the curve (AUC) for prediction of asthma at (i) 18 and (ii) 26 years, and persistent asthma (PA) (iii) at 10 and 18 years, and (iv) at 10, 18 and 26 years. Models were internally and externally validated. Results Four models were generated for prediction of each asthma outcome. ASthma PredIctive Risk scorE (ASPIRE)‐1: a 2‐factor model (recurrent wheeze [RW] and positive skin prick test [+SPT] at 4 years) for asthma at 18 years (sensitivity: 0.49, specificity: 0.80, AUC: 0.65). ASPIRE‐2: a 3‐factor model (RW, +SPT and maternal rhinitis) for asthma at 26 years (sensitivity: 0.60, specificity: 0.79, AUC: 0.73). ASPIRE‐3: a 3‐factor model (RW, +SPT and eczema at 4 years) for PA‐18 (sensitivity: 0.63, specificity: 0.87, AUC: 0.77). ASPIRE‐4: a 3‐factor model (RW, +SPT at 4 years and recurrent chest infection at 2 years) for PA‐26 (sensitivity: 0.68, specificity: 0.87, AUC: 0.80). ASPIRE‐1 and ASPIRE‐3 scores were replicated externally. Further assessments indicated that ASPIRE‐1 can be used in place of ASPIRE‐2‐4 with same predictive accuracy. Conclusion ASPIRE predicts persistent asthma up to young adult life.
The triangular relationship between traditional Chinese medicines, intestinal flora, and colorectal cancer
Authors: Yuqing Zou, Shuling Wang, Honghua Zhang, Yuxin Gu, Huijuan Chen, Zhihua Huang, Feifei Yang, Wenqi Li, Cheng Chen, Lianhui Men, Qingchang Tian, Tian Xie
Journal: Medicinal Research Reviews (2023)

Abstract Over the past decade, colorectal cancer has reported a higher incidence in younger adults and a lower mortality rate. Recently, the influence of the intestinal flora in the initiation, progression, and treatment of colorectal cancer has been extensively studied, as well as their positive therapeutic impact on inflammation and the cancer microenvironment. Historically, traditional Chinese medicine (TCM) has been widely used in the treatment of colorectal cancer via promoted cancer cell apoptosis, inhibited cancer metastasis, and reduced drug resistance and side effects. The present research is more on the effect of either herbal medicine or intestinal flora on colorectal cancer. The interactions between TCM and intestinal flora are bidirectional and the combined impacts of TCM and gut microbiota in the treatment of colon cancer should not be neglected. Therefore, this review discusses the role of intestinal bacteria in the progression and treatment of colorectal cancer by inhibiting carcinogenesis, participating in therapy, and assisting in healing. Then the complex anticolon cancer effects of different kinds of TCM monomers, TCM drug pairs, and traditional Chinese prescriptions embodied in apoptosis, metastasis, immune suppression, and drug resistance are summarized separately. In addition, the interaction between TCM and intestinal flora and the combined effect on cancer treatment were analyzed. This review provides a mechanistic reference for the application of TCM and intestinal flora in the clinical treatment of colorectal cancer and paves the way for the combined development and application of microbiome and TCM.
The Origin of the Intracellular Silver in Bacteria: A Comprehensive Study using Targeting Gold–Silver Alloy Nanoparticles
Authors: Carmen Streich, Frederic Stein, Jurij Jakobi, Alexandra Ingendoh‐Tsakmakidis, Nils Heine, Christoph Rehbock, Andreas Winkel, Sebastian Grade, Mark Kühnel, Vadim Migunov, András Kovács, Thomas Knura, Meike Stiesch, Bernd Sures, Stephan Barcikowski
Journal: Advanced Healthcare Materials (2023)

Abstract The bactericidal effects of silver nanoparticles (Ag NPs) against infectious strains of multiresistant bacteria is a well‐studied phenomenon, highly relevant for many researchers and clinicians battling bacterial infections. However, little is known about the uptake of the Ag NPs into the bacteria, the related uptake mechanisms, and how they are connected to antimicrobial activity. Even less information is available on AgAu alloy NPs uptake. In this work, the interactions between colloidal silver–gold alloy nanoparticles (AgAu NPs) and Staphylococcus aureus ( S. aureus ) using advanced electron microscopy methods are studied. The localization of the nanoparticles is monitored on the membrane and inside the bacterial cells and the elemental compositions of intra‐ and extracellular nanoparticle species. The findings reveal the formation of pure silver nanoparticles with diameters smaller than 10 nm inside the bacteria, even though those particles are not present in the original colloid. This finding is explained by a local RElease PEnetration Reduction (REPER) mechanism of silver cations emitted from the AgAu nanoparticles, emphasized by the localization of the AgAu nanoparticles on the bacterial membrane by aptamer targeting ligands. These findings can deepen the understanding of the antimicrobial effect of nanosilver, where the microbes are defusing the attacking silver ions via their reduction, and aid in the development of suitable therapeutic approaches.
Challenge‐verified thresholds for allergens mandatory for labeling: How little is too much for the most sensitive patient?
Authors: Charlotte G. Mortz, Esben Eller, Olav Sivertsen Garvik, Henrik Fomsgaard Kjaer, Torsten Zuberbier, Carsten Bindslev‐Jensen
Journal: Allergy (2023)

Abstract Background It is mandatory to label food products with the 14 main allergens in the EU. Reasonable allergen labeling requires knowledge of population‐based thresholds derived from food challenges. The aim of this study was to evaluate the threshold‐distribution in clinically verified food allergic patients for allergens mandatory for labeling. Methods All positive open oral food challenges and double‐blind placebo‐controlled food challenges (DBPCFC) performed at the Allergy Center, Odense University Hospital, Denmark (2000–2022) were included. For each included challenge, the cumulative threshold (LOAEL) was obtained and NOAEL estimated. Data were modelled as an interval censored log‐normal distribution. Results Overall, 38 of all 2612 challenges (1.5%) in 1229 patients (717 male, 986 children) reacted to &lt;5 mg protein. The majority of the most sensitive patients reacted with a Sampson severity score of 2–3. Using interval censored log‐normal models only five groups (hens´ egg, fish, peanut, milk, tree‐nuts) elicited reactions after ingestion of 0.5 mg protein and in low frequencies of the population. Hen's egg was the most potent allergen, with reactivity to &lt;0.5 mg protein in 0.24% [0.13–0.44%] of egg allergic patients while the estimated fraction of allergic patients reacting to a eliciting dose on 0.5 mg protein for most other allergens were below 0.04%. Conclusion Our data demonstrates that the majority of food allergic patients as expected tolerating traces of allergenic foods without developing severe allergic symptoms and signs. Hen's egg appears to be the food most likely to elicit reactions in the most sensitive individuals at very low doses.
PhyloAcc-GT: A Bayesian Method for Inferring Patterns of Substitution Rate Shifts on Targeted Lineages Accounting for Gene Tree Discordance
Authors: Han Yan, Zhirui Hu, Gregg W C Thomas, Scott V Edwards, Timothy B Sackton, Jun S Liu
Journal: Molecular Biology and Evolution (2023)

An important goal of evolutionary genomics is to identify genomic regions whose substitution rates differ among lineages. For example, genomic regions experiencing accelerated molecular evolution in some lineages may provide insight into links between genotype and phenotype. Several comparative genomics methods have been developed to identify genomic accelerations between species, including a Bayesian method called PhyloAcc, which models shifts in substitution rate in multiple target lineages on a phylogeny. However, few methods consider the possibility of discordance between the trees of individual loci and the species tree due to incomplete lineage sorting, which might cause false positives. Here, we present PhyloAcc-GT, which extends PhyloAcc by modeling gene tree heterogeneity. Given a species tree, we adopt the multispecies coalescent model as the prior distribution of gene trees, use Markov chain Monte Carlo (MCMC) for inference, and design novel MCMC moves to sample gene trees efficiently. Through extensive simulations, we show that PhyloAcc-GT outperforms PhyloAcc and other methods in identifying target lineage-specific accelerations and detecting complex patterns of rate shifts, and is robust to specification of population size parameters. PhyloAcc-GT is usually more conservative than PhyloAcc in calling convergent rate shifts because it identifies more accelerations on ancestral than on terminal branches. We apply PhyloAcc-GT to two examples of convergent evolution: flightlessness in ratites and marine mammal adaptations, and show that PhyloAcc-GT is a robust tool to identify shifts in substitution rate associated with specific target lineages while accounting for incomplete lineage sorting.
Reducing the risks of nuclear war: the role of health professionals
Authors: Kamran Abbasi, Parveen Ali, Virginia Barbour, Kirsten Bibbins-Domingo, Marcel GM Olde Rikkert, Andy Haines, Ira Helfand, Richard Horton, Bob Mash, Arun Mitra, Carlos Monteiro, Elena N Naumova, Eric J Rubin, Tilman Ruff, Peush Sahni, James Tumwine, Paul Yonga, Chris Zielinski
Journal: Journal of the Royal Society of Medicine (2023)
Nicotinamide for skin cancer chemoprevention in transplant recipients: a critically appraised topic
Authors: Ashley O Riddle, Anokhi Jambusaria-Pahlajani
Journal: British Journal of Dermatology (2023)

This paper critically appraises a phase III trial examining the impact of oral nicotinamide on reducing keratinocyte carcinoma (KC) incidence in solid organ transplant recipients. Despite a well-conducted study finding no significant difference in KC rates between nicotinamide and placebo groups, we suggest that the conclusion could be premature due to the study’s underpowered sample size and lack of analysis on more invasive cancers.
Metaverse Surgical Planning with Three-dimensional Virtual Models for Minimally Invasive Partial Nephrectomy
Authors: Enrico Checcucci, Daniele Amparore, Gabriele Volpi, Sabrina De Cillis, Federico Piramide, Paolo Verri, Alberto Piana, Michele Sica, Cecilia Gatti, Paolo Alessio, Alberto Quarà, Mariano Burgio, Marco Colombo, Giovanni Busacca, Alex Mottrie, Edward Cherullo, Alberto Breda, Alessandro Antonelli, Renaud Bollens, Andrea Minervini, James Porter, Riccardo Schiavina, Riccardo Autorino, Ashutosh Tewari, Michele Di Dio, Cristian Fiori, Francesco Porpiglia
Journal: European Urology (2023)
Elevated symptoms of depression and anxiety among family members and friends of critically ill COVID-19 patients – an observational study of five cohorts across four countries
Authors: Anikó Lovik, Juan González-Hijón, Asle Hoffart, Chloe Fawns-Ritchie, Ingibjörg Magnúsdóttir, Li Lu, Anna Bára Unnarsdóttir, Anna K. Kähler, Archie Campbell, Arna Hauksdóttir, Charilaos Chourpiliadis, Daniel L. McCartney, Edda Björk Thordardóttir, Emily E. Joyce, Emma M. Frans, Jóhanna Jakobsdóttir, Lill Trogstad, Ole A. Andreassen, Per Magnus, Sverre Urnes Johnson, Patrick F. Sullivan, Thor Aspelund, David J. Porteous, Helga Ask, Omid V. Ebrahimi, Unnur Anna Valdimarsdóttir, Fang Fang
Journal: The Lancet Regional Health - Europe (2023)

Little is known regarding the mental health impact of having a significant person (family member and/or close friend) with COVID-19 of different severity.The study included five prospective cohorts from four countries (Iceland, Norway, Sweden, and the UK) with self-reported data on COVID-19 and symptoms of depression and anxiety during March 2020-March 2022. We calculated prevalence ratios (PR) of depression and anxiety in relation to having a significant person with COVID-19 and performed a longitudinal analysis in the Swedish cohort to describe temporal patterns.162,237 and 168,783 individuals were included in the analysis of depression and anxiety, respectively, of whom 24,718 and 27,003 reported a significant person with COVID-19. Overall, the PR was 1.07 (95% CI: 1.05-1.10) for depression and 1.08 (95% CI: 1.03-1.13) for anxiety in relation to having a significant person with COVID-19. The respective PRs for depression and anxiety were 1.15 (95% CI: 1.08-1.23) and 1.24 (95% CI: 1.14-1.34) if the patient was hospitalized, 1.42 (95% CI: 1.27-1.57) and 1.45 (95% CI: 1.31-1.60) if the patient was ICU-admitted, and 1.34 (95% CI: 1.22-1.46) and 1.36 (95% CI: 1.22-1.51) if the patient died. Individuals with a significant person with hospitalized, ICU-admitted, or fatal COVID-19 showed elevated prevalence of depression and anxiety during the entire year after the COVID-19 diagnosis.Family members and close friends of critically ill COVID-19 patients show persistently elevated prevalence of depressive and anxiety symptoms.This study was primarily supported by NordForsk (COVIDMENT, 105668) and Horizon 2020 (CoMorMent, 847776).
Estimating the exposure–response function between long-term ozone exposure and under-5 mortality in 55 low-income and middle-income countries: a retrospective, multicentre, epidemiological study
Authors: Tao Xue, Ruohan Wang, Mingkun Tong, Frank J Kelly, Hengyi Liu, Jiajianghui Li, Pengfei Li, Xinghua Qiu, Jicheng Gong, Jing Shang, Tong Zhu
Journal: The Lancet Planetary Health (2023)

BackgroundIn 2021, WHO suggested new target concentration limits for long-term exposure to ambient ozone. However, the harmful effects of ozone on vulnerable children have not been sufficiently studied. We aimed to evaluate the association between long-term ozone exposure and mortality in children younger than 5 years (hereafter denoted under-5 mortality) in low-income and middle-income countries (LMICs) and to estimate this mortality burden for 97 LMICs.MethodsBy combining information from 128 Demographic and Health Surveys, we evaluated the association between the survival status of more than 1·2 million children younger than 5 years from 2457 sampling strata in 55 LMICs and the average peak-season ozone concentration during the life course, using a fixed-effects Cox model. A non-linear exposure–response function was developed by integrating the marginal effects of within-strata variation in exposure. We extrapolated the function obtained from the 55 LMICs to estimate the under-5 mortality burden attributable to ozone exposure in 97 LMICs, in which more than 95% of global deaths in this age group occur.FindingsThe fixed-effects model showed a robust association between ozone and under-5 mortality. According to the fully adjusted linear model, an increment of 10 ppb in the life-course average peak-season ozone concentration was associated with a 6·4% (95% CI 2·4–10·7) increase in the risk of under-5 mortality. The non-linear exposure–response function showed a sublinear curvature with a threshold, suggesting that the effect of ozone exposure was non-significant at concentrations lower than the first-stage interim target (100 μg/m3) recommended by WHO. Using this function, we estimate that, in 2010, long-term ozone exposure contributed to 153 361 (95% CI 17 077–276 768; 2·3% [0·3–4·1]) deaths of children younger than 5 years in 97 LMICs, which is equivalent to 56·8% of all ozone-related deaths in adults (269 785) in these countries. From 2003 to 2017, the ozone-related under-5 mortality burden decreased in most of the 97 LMICs.InterpretationLong-term exposure to ozone concentrations higher than the WHO first-stage interim target is a risk factor for under-5 mortality, and ozone exposure contributes substantially to mortality in this age group in LMICs. Increased efforts should be made to control ambient ozone pollution as this will lead to positive health benefits.FundingMinistry of Science and Technology of the People's Republic of China and China National Natural Science Foundation.
The skin barrier: An extraordinary interface with an exceptional lipid organization
Authors: Joke A. Bouwstra, Andreea Nădăban, Wim Bras, Clare McCabe, Annette Bunge, Gerrit S. Gooris
Journal: Progress in Lipid Research (2023)

The barrier function of the skin is primarily located in the stratum corneum (SC), the outermost layer of the skin. The SC is composed of dead cells with highly organized lipid lamellae in the intercellular space. As the lipid matrix forms the only continuous pathway, the lipids play an important role in the permeation of compounds through the SC. The main lipid classes are ceramides (CERs), cholesterol (CHOL) and free fatty acids (FFAs). Analysis of the SC lipid matrix is of crucial importance in understanding the skin barrier function, not only in healthy skin, but also in inflammatory skin diseases with an impaired skin barrier. In this review we provide (i) a historical overview of the steps undertaken to obtain information on the lipid composition and organization in SC of healthy skin and inflammatory skin diseases, ii) information on the role CERs, CHOL and FFAs play in the lipid phase behavior of very complex lipid model systems and how this knowledge can be used to understand the deviation in lipid phase behavior in inflammatory skin diseases, iii) knowledge on the role of both, CER subclasses and chain length distribution, on lipid organization and lipid membrane permeability in complex and simple model systems with synthetic CERs, CHOL and FFAs, iv) similarity in lipid phase behavior in SC of different species and complex model systems, and vi) future directions in modulating lipid composition that is expected to improve the skin barrier in inflammatory skin diseases.
Patients with telomere biology disorders show context specific somatic mosaic states with high frequency of <scp><i>U2AF1</i></scp> variants
Authors: Alejandro Ferrer, Terra Lasho, Jenna A. Fernandez, Nickolas P. Steinauer, Rachel A. Simon, Christy M. Finke, Eva M. Carmona, Mark E. Wylam, Laura J. Ongie, Brittany N. Burnap, Cecilia Arana Yi, Lisa Z. Sproat, James Foran, Talha Badar, Abhishek A. Mangaonkar, Mrinal M. Patnaik
Journal: American Journal of Hematology (2023)

Somatic mosaic states in telomere biology disorders are characterized by somatic variants in the spliceosome and DNA damage response and repair pathways. A likely maladaptive response to short telomeres that may lead to increased hematological cancer.